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Overarching themes of the NIH Roundtable reports included: • Emergency care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. • Rapidly identifying the phenotype of patients manifesting a specific disease process, and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency care research. • Need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical illnesses and injuries, and the development of treatments capable of halting or reversing them. • Need for novel experimental models of emergency conditions. • Understand regional differences in outcome for the same emergency disease processes. In addition, a number of important barriers to emergency care research were identified in the NIH Roundtable reports, including: • Limited number of trained investigators and experienced mentors in emergency care research. • Limited emergency care research infrastructure and support, and regulatory hurdles. The NIH Roundtables recommended that the science of emergency care may be advanced by facilitating the following: (a) training of emergency care investigators; (b) development of emergency care clinical research networks; (c) emergency care–specific federal research initiatives; (d) involvement of emergency specialists in grant review and research advisory processes; (e) support learn-phase and adaptive clinical trials; and (f) performance of research to address unique ethical and regulatory issues in emergency research. CONCLUSIONS Emergency medicine research involves the study of time-sensitive, severe disease conditions that impact broad populations. The hypothesis that time makes a difference has been proven in multiple emergency conditions. These successes have led to the development of a compelling research agenda for emergency care. Enhancement of the research basis for emergency care will require progress in mechanistic, translational, and clinical domains as well as collaboration of investigators across traditional clinical and scientific disciplines. In addition, emergency care researchers will need to overcome limitations in available infrastructure, research training, and access to emergency patient populations.